Katsuyuki Takeda;Nobuaki Miyahara;Shigeki Matsubara;Christian Taube;Kenichi Kitamura;Astushi Hirano;Mitsune Tanimoto;Erwin W. Gelfand
IMMUNE NETWORK
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v.16
no.3
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pp.165-175
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2016
Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.
Background: Costimulation is a critical process in Ag-specific immune responses. Both B7.1 and CD28 molecules have been reported to stimulate T cell responses during antigen presentation. Therefore, we tested whether Ag-specific immune responses as well as protective immunity are influenced by coinjecting with B7.1 and CD28 cDNAs in a mouse HSV-2 challenge model system. Methods: ELISA was used to detect levels of antibodies, cytokines and chemokines while thymidine incorporation assay was used to evaluate T cell proliferation levels. Results: Ag-specific antibody responses were enhanced by CD28 coinjection but not by B7.1 coinjection. Furthermore, CD28 coinjection increased IgG1 production to a significant level, as compared to pgD+pcDNA3, suggesting that CD28 drives Th2 type responses. In contrast, B7.1 coinjection showed the opposite, suggesting a Th1 bias. B7.1 coinjection also enhanced Ag-specific Th cell proliferative responses as well as production of Th1 type cytokines and chemokines significantly higher than pgD+pcDNA3. However, CD28 coinjection decreased Ag-specific Th cell proliferative responses as well as production of Th1 types of cytokines and chemokine significantly lower than pgD+pcDNA3. Only MCP-1 production was enhanced by CD28. B7.1 coimmunized animals exhibited an enhanced survival rate as well as decreased herpetic lesion formation, as compared to pgD+pcDNA3. In contrast, CD28 vaccinated animals exhibited decreased survival from lethal challenge. Conclusion: This study shows that B7.1 enhances protective Th1 type cellular immunity against HSV-2 challenge while CD28 drives a more detrimental Th2 type immunity against HSV-2 challenge, supporting an opposite role of B7.1 and CD28 in Ag-specific immune responses to a Th1 vs Th2 type.
The methods that make Hantavirus grow consist of inoculation into the experimental animals and cultured cells. The cultured cells, such as Vero-E6 and A549 cells, have been usually used for isolation of the virus and the animals, such as mice and rats, are used for large scale preparation of the virus so far. Furthermore, the cell can be used to maintain the virus and assay the infectivity and the animals can be used for the experiment of viral pathogenicity and challenge for assessment of vaccine. Apodemus mice, the own natural host of the virus, has been used for challenge test of Hantaan virus. However it has been pointed out to difficult handling and breeding the animal in laboratory. Therefore, we attempted to establish a new animal model for challenge test at the time of isolation of Maaji virus which is a new hantavirus similar but distinct to Hantaan virus. In suckling hamster, the titer of Maaji virus and the lethality to mice of the virus were increased gradually in the titer and lethality through passage by intracerebral (IC) inoculation. We tried to re-adapt this brain virus to lung of weanling hamster. The brain passaged virus was inoculated into weanling hamster intramuscularly. Again, the titer of the virus in lung was also increased by continuous passage of this virus. This facts could regarded as adaptation to new environment in which the virus proliferates. To identity the virus passaged in hamster with Maaji virus, both of the virus passaged in hamster brain and lung were compared with Maaji virus (MAA-I) and Hantaan virus (HTN 76-118) by means of restriction fragment length polymorphism (RFLP) and slingle strand conformation polymophism (SSCP). As a result, we conclude that Maaji virus could be adapted successfully to weanling hamster through this passage strategy. Utilizing this adapted Maaji virus strain, hamster model is able to be used for challenge test in hantaviral vaccinology and further experiments utilizing hamster system as a rather available and convenient lab animal are expected.
Post-weaning diarrhea (PWD), mostly caused by enterotoxigenic Escherichia coli (ETEC), remains to be a major source of economic loss in swine industry. The use of the ETEC-oral challenge model is often applied to mimic unsanitary commercial swine farm conditions where pathogens and unknown complex microbes exist and can cause severe infections in pigs. The purpose of this study was (1) to estimate ETEC density using spectrophotometric computation, (2) to determine survivability of ETEC after storing at $-20^{\circ}C$ for 7 days, and (3) to evaluate survivability of ETEC after blending with diluted sweeteners (0, 5, 10, 20, and 40% sucrose in phosphate buffered saline [PBS]). Cell density was quantified using UV-VIS spectrophotometer and counting ETEC colony forming units (cfu) at 0, 30, 60, 90, 120, 150, 180, 210, and 240 min. The established linear equation ($y=0.0031x^2-0.0079x+0.0043$ and $y=0.0046x^2-0.0151x+0.0113$) was used for robust quantification of each ETEC cell density. ETEC stored at $-20^{\circ}C$ showed 108 cfu/mL after thawing and incubation. When ETEC was blended with sweeteners (20 and 40%), survival of ETEC was decreased by 58 and 54% in 5 min post blending. However, addition of 20% of sweetener resulted in a higher survivability than those with other media concentrations. Therefore, the use of ETEC-oral challenge model would be possible as a stable method if we could confirm the appropriate medium that increases survivability of ETEC in weaner pigs.
Journal of Information Technology Applications and Management
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v.27
no.6
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pp.197-224
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2020
Mobile games have become one of the most important driving forces of the game industry. We focus on the continuous intention to use Chinese mobile games from the perspective of experiential marketing and network externalities. We integrate user experience, network externalities and flow theory into expectation confirmation model and explore the influencing factors of continuous usage intention of Chinese mobile game and propose a research model. Game experience, service experience, perceived enjoyment, social interaction, challenge, perceived number of users and perceived number of peers were employed as independent variables, while flow, perceived value and satisfaction as mediating variables and continuous intention as the dependent variable. After surveying 426 samples, the model is tested with structural equation model. The results reveal that perceived enjoyment significantly positively influences perceived value, flow, satisfaction, and continuous intention. The greater the enjoyment of the game, the greater the satisfaction of the game and the greater the willingness to use it continuously. Game experience has a significant direct effect on continuous intention, which indicates that a better game experience can retain more users. Service experience and perceive number of peers positively influence satisfaction. Another finding is that social interaction and perceived number of users positively influence perceived value and flow, which indicate that social attributes are critical roles for retaining users. Game challenge also positively influences flow. The proper level of challenge is more likely to cause users to enter the state of flow. Flow indirectly influences continuous usage intention through the satisfaction of the game, which indicates that satisfaction is driven by flow experience and further retaining users. Empirical results implied that mobile game companies need to focus on improving user experience, expectation satisfaction and extending network externalities to improve the continuous intention of using mobile game.
The biggest characteristic of Social Network Game(SNG) is that games are played through competition and cooperation with the actual acquaintances based on SNS. Even though such competition and challenge spirit have been dealt importantly as preceding factors having influence on the flow in games in the existing game area, it is rare to find researches deeply considering the characteristics of ranking competition between acquaintances in SNG. Moreover, it was not considered that such acquaintances could be the targets of competition and also challenge at the same time in SNG. Therefore, this study examined the achievements(big differences in ranking, small differences in ranking) of the targets for comparison and closeness(strong ties, weak ties) with the targets for comparison as factors having influence on competition and challenge spirit, and also empirically analyzed the influence of such factors and interactions between factors on players' competition and challenge spirit in the ranking competitive society, by analyzing the characteristics of ranking competition between acquaintances in the mobile puzzle, SNG based on SNS through the analysis on the preceding research on the self-evaluation maintenance model of the social comparison theory. In the results, when preferentially exposing competitors with small difference in ranking and also exposing competitors with stronger ties, players' competition is stimulated, so that it can improve their challenge spirit. Such results of this study can be expected to a lot contribute to the actual design work of SNG ranking table contents.
This study was undertaken to develop a reliable mice model demonstrating similar immunologic phenomena as human atopic dermatitis characterized with predominance of type-2 immune response. BALB/C mice and NC/Nga mice were sensitized twice with $100{\mu}l$ of 1% 2,4-dinitrochlorobenzene (DNCB) or vehicle (acetone : olive oil=4:1 mixture) in a week and challenged twice with $100{\mu}l$ of 0.2% DNCB or the vehicle at the following week. Mice were sacrificed at 19 days following the second DNCB or vehicle challenge for NC/Nga mice and at 28 days following the second DNCB or vehicle challenge for BALB/c mice. Upregulation of plasma 1gE, a hallmark of atopic dermatitis occurrence, was evident in the plasma obtained 4 day after the second DNCB challenge from BALB/c mice (approximately 4-fold) and NC/Nga mice (approximately 6-fold) treated with DNCB in comparison with that of the vehicle treated-control mice, and remain higher $3{\sim}4$ week after the second challenge. Ratio of plasma IgG1 versus IgG2a concentration was significantly higher in the mice treated with DNCB than the control mice, which also implies the skewed type-2 reactivity in vivo. Ratio of interleukin-4 versus interferon gamma produced in the splenic T cell culture supernatants was approximately 3-fold higher in the both strains of mice treated with DNCB than their control mice, respectively. The DNCB-treated mice demonstrated atopic dermatitis-like skin legions characterized with erythma, scaling, and hemorrhage, which was not observed with the control mice. Scratching on face or dorsal area was significantly more frequent (approximately 25-fold) in the DNCB-treated mice than the control at next day of the second DNCB challenge, and scratching frequency remains higher (approximately 4-fold) in the mice treated with DNCB than the control at 14 day following the second DNCB challenge. Overall, the mice model developed through sensitization and challenge with DNCB may be useful for research on atopic dermatitis and development of treatment materials for atopic dermatitis.
Journal of the Korea Society of Computer and Information
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v.17
no.11
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pp.163-171
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2012
Many previous researches in the area of online games have been carried out about internet addiction by psychologist and about the development of related technologies by scientists. There are a few studies about the consumer satisfaction from the online business model. The purpose of this study is to examine the causal relationship between critical factors and consumer satisfaction of online game users. This study model used five themes(interactivity, enjoyment, challenge, feedback, design) in order to identify the effect of critical factors on consumer satisfaction. The result of this study identified that interactivity, enjoyment, challenge have a significant effect on consumer satisfaction of online game users. Future areas for studying on the Effect of Critical Factors on Consumer Satisfaction of Online Game Users are continuously discussed.
Kim, M.H.;Yun, C.H.;Kim, G.R.;Ko, J.Y.;Lee, Jung-Joo;Ha, Jong-K.
Asian-Australasian Journal of Animal Sciences
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v.24
no.5
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pp.696-706
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2011
The objective of this study was to characterize serum immunoglobulins and lymphocytes subpopulations in the peripheral blood mononuclear cells (PBMCs) of Holstein calves in response to lipopolysaccharide (LPS) challenge from Escherichia coli. Fourteen calves received subcutaneous injections of E. coli LPS at 10 weeks of age, and six calves were injected with saline as a control. The concentrations of total serum IgG and the relative amount of LPS-specific IgG in calves challenged with LPS were significantly higher (p<0.05) compared to control animals and LPS challenge significantly increased (p<0.05) the percentage of $CD5^+$ and $CD21^+$ T cells in PBMCs. Meanwhile, LPS challenge significantly increased (p<0.05, p<0.01) the percentage of $CD8^+$ and $CD25^+$ T cells in peripheral blood mononuclear cells (PBMC) at 7 and 14 Day-post LPS challenge (DPLC), respectively. The composition of $CD4^+CD25^+$ T cells and $CD8^+CD25^+$ T cells from calves challenged with LPS was also higher (p<0.05 and p = 0.562, respectively) than those of control calves at 14 DPLC. In conclusion, LPS challenge not only induces production of IgG with expression of B-cell immune response related cell surface molecules, but also stimulates activation of T-lymphocytes in PBMC. Our results suggest that LPS challenge in calves is a good model to elucidate cellular immune response against Gram-negative bacterial infections.
The hybrid fault diagnosis method based on a combination of the signed digraph (SDG) and the partial least-squares (PLS) has the advantage of improving the diagnosis resolution, accuracy and reliability, compared to those of previous qualitative methods, and of enhancing the ability to diagnose multiple fault. In this study, the method is applied for the multiple fault diagnosis of the Tennessee Eastman challenge process, which is a realistic industrial process for evaluating process contol and monitoring methods. The process is decomposed using the local qualitative relationships of each measured variable. Dynamic PLS (DPLS) model is built to estimate each measured variable, which is then compared with the estimated value in order to diagnose the fault. Through case studies of 15 single faults and 44 double faults, the proposed method demonstrated a good diagnosis capability compared with previous statistical methods.
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